Kelesidis Theodoros, Tran Thuy Tien T, Stein James H, Brown Todd T, Moser Carlee, Ribaudo Heather J, Dube Michael P, Murphy Robert, Yang Otto O, Currier Judith S, McComsey Grace A
David Geffen School of Medicine at the University of California, Los Angeles.
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Clin Infect Dis. 2015 Aug 15;61(4):651-60. doi: 10.1093/cid/civ327. Epub 2015 Apr 22.
It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs).
In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control.
Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups.
Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens.
NCT00811954 and NCT00851799.
与利托那韦增强的蛋白酶抑制剂（PIs）相比，整合酶抑制剂拉替拉韦（RAL）是否能减轻炎症和免疫激活尚不清楚。
在一项前瞻性、随机、多中心临床试验中，328名未接受过治疗的1型人类免疫缺陷病毒（HIV-1）感染者被随机分为接受替诺福韦酯-恩曲他滨（TDF/FTC）加阿扎那韦/利托那韦（ATV/r）、达芦那韦/利托那韦（DRV/r）或RAL治疗。共有234名在第24周时HIV-1 RNA水平<50拷贝/mL的参与者（71%）被纳入研究。分析的血浆炎症和凝血生物标志物包括高敏C反应蛋白、白细胞介素-6（IL-6）、GlycA、D-二聚体、可溶性CD14（sCD14）、sCD163和sIL-2r；血细胞标志物包括T细胞亚群的%CD38+DR+以及单核细胞亚群的%CD14+CD16+和%CD14(dim)CD16+。在早期（24或48周）和晚期（96周）时间点检查相对于基线的变化，并给出95%置信区间的变化倍数。使用Wilcoxon秩和检验比较各治疗组，P值经错误发现率控制调整。
在96周的随访期间，生物标志物的变化因治疗方案而异，具体如下：hsCRP随ATV/r和RAL下降，IL-6仅随RAL下降，所有组的GlycA均降低。D-二聚体随ATV/r和DRV/r下降，随RAL无变化。所有组的T细胞激活标志物和sCD163（但不包括sCD14和CD14+CD16+）均下降。
尽管抗逆转录病毒治疗（ART）方案在炎症和免疫激活的特定标志物方面存在一些差异，但我们没有发现一致的证据表明RAL方案和基于PI的方案在开始ART治疗时减轻炎症和免疫激活方面存在差异。
NCT00811954和NCT00851799。
